Synthesis of a New Inotropic Steroid Derivative and its Relationship with log P, p, Rm, Vm, Pc, St

Abstract

In this work, a new inotropic steroid derivative was synthesized. The route involved preparation of furosemide-pregnenolone derivative by the reaction of furosemide with pregnenolone-succinate- ethylenediamine conjugate using a carbodiimide as catalyst. The biological activity of furosemide-pregnenolone and pregnenolone-succinate-ethylenediamine was evaluated in isolated rat hearts using Langendonff model. To delineate the structural chemical requirements of furosemide-pregnenolone as inotropic agent, other parameters such as the physicochemical descriptors log P, p, R_m, V_m, P_c and S_t were calculated. The results showed that the furosemidepregnenolone derivative significantly increase the perfusion pressure (p = 0.006), coronary resistance (p = 0.005) and intracellular calcium (1.35 × 10^-3 to 2.70 × 10^-3 mM) in isolated heart. Additionally, other data indicate that values of log P, p, R_m, V_m, P_c and S_t are high in the furosemidepregnenolone in comparison with pregnenolone-succinate-ethylenediamine. These data suggest that functional groups involved in the structure of furosemide-pregnenolone are specific for their positive inotropic activity.